Main mutation site of the coronavirus variant B.1.531 emerged in South Africa. The spike protein (red) is bound to the angiotensin converting enzyme 2 (blue). The mutation is at the amino acid position 484 (yellow).
With variants of SARS-Co-V2 arising in Europe, South Africa and Brazil causing alarm about the efficacy of the current vaccines, a number of researchers at Penn Medicine and the Perelman School of Medicine — including Paul A. Offit, MD,Susan R. Weiss, PhD, and Drew Weissman, MD, PhD — have offered their insight on the issue.
COVID-19 Vaccines Efficacy Against Vaccine Variants
In a recent interview with JAMA network, Dr. Offit noted that the speed with which variants have appeared as dominant strains in the UK, South Africa and Brazil is a reflection of viral adaptation for growth in the human population. An infectious disease specialist with Penn's Perelman School of Medicine and the Children's Hospital of Philadelphia, Dr. Offit is a member of the Vaccines and Related Biological Products Advisory Committee for the Food and Drug Administration.
"It's reasonable to be concerned about the variants, because this virus continues to drift at some level," Dr. Offit said. "We should worry when people who have been naturally infected or have completed the immunization series are nonetheless less hospitalized with one of these variants. This hasn't happened yet."
Deletions and Substitutions: How do Mutations Work to Alter Viral Attributes?
Mutations are the engine of evolution for viruses, and rate of mutation has been correlated with pathogenesis and the emergence of new diseases. Generally, the single-stranded RNA viruses (including SARS-CoV2) display the fastest rate of mutation — faster than double-stranded RNA viruses, and faster still than DNA viruses.
Mutations at the S protein that increase viral shedding or affinity for the ACE-2 receptor or change the shape of the protein and its neutralizing antibody (Nab) binding sites would be expected to increase viral transmission. This could thus play a role in the demarcation between optimal and suboptimal vaccine efficacy. There is a fear that "escape" mutations arising in the wake of COVID vaccines that limit, but do not eradicate, viral replication could result in a strain that spreads more quickly and efficiently.
The virus that escaped China in early 2020 or late 2019 was a descendant of Wuhan-Hu1, the original, or reference, strain of SARS-CoV-2. This variant, called D614G, contained a single substitution in its genome that made it much more transmissible — a goal that fits the natural history of all viruses. Later variant strains of SARS-CoV-2, including B117 in the UK and the South African (B1351) and Brazilian (P1) variants, are descendants of D614G.
Speaking recently at a seminar for the University of Pennsylvania's Perry World House presentation, Dr. Susan R. Weiss discussed the variants and their potential for risk.
"Most of these variants… are not the result of immune evasion," she explained. "Viruses change all the time, particularly RNA viruses, and the more time they have to replicate, the more they're going to change — and they're going change in a way that allows them to replicate better."
The standard for vaccines to achieve, Dr. Offit said, is sufficient protection to protect individuals against serious disease and its consequence, hospitalization. To date, the vaccines developed to treat D614G⏤and that would be all of them at the moment — are maintaining a degree of efficacy against evolving variants of the virus that meets this standard.
"What you want from a vaccine is one that keeps you out of the hospital, keeps you out of the ICU and keeps you from dying, and that's what these vaccines do," Dr. Offit explained.
mRNA: Plug and Play
In a JAMA article published in late January, Dr. Offit outlined the advantages of the mRNA vaccines, including their induction of virus-specific helper and killer T-cells, both of which may contribute to protection, and a strong NAb response that there could be sufficient to deal with reductions in the sensitivity of the variants to NAbs.
A further advantage for the mRNA vaccines, says Dr. Drew Weissman, of the Perelman School of Medicine, is that the design of the mRNA vaccines can be adjusted to accommodate viral sequence changes as they arise.
"It's literally plug and play," Dr. Weissman said in a recent interview. "Once you have the sequence of a new variant, you put it in the same RNA the original virus comes from, and you've made a new vaccine."
Dr. Weissman, who co-developed the technology that made the mRNA vaccines possible, is currently working on a multivalent vaccine to cover all current and future variants at the University of Pennsylvania.
"Nobody wants to be in a position where a variant is suddenly infecting everybody all over again," he said in a recent interview. "We haven't hit that point. So we've got time to do this right."
COVID-19 Vaccines: Additional Penn Resources